Activation of D1/D5 dopamine receptors protects neurons from synapse dysfunction induced by amyloid-beta oligomers

Soluble oligomers of the amyloid-β peptide (AβOs) accumulate in the brains of Alzheimer disease (AD) patients and are implicated in synapse failure and early memory loss in AD. AβOs have been shown to impact synapse function by inhibiting long term potentiation, facilitating the induction of long term depression and inducing internalization of both AMPA and NMDA glutamate receptors, critical players in plasticity mechanisms. Because activation of dopamine D1/D5 receptors plays important roles in memory circuits by increasing the insertion of AMPA and NMDA receptors at synapses, we hypothesized that selective activation of D1/D5 receptors could protect synapses from the deleterious action of AβOs. We show that SKF81297, a selective D1/D5 receptor agonist, prevented the reduction in surface levels of AMPA and NMDA receptors induced by AβOs in hippocampal neurons in culture. Protection by SKF81297 was abrogated by the specific D1/D5 antagonist, SCH23390. Levels of AMPA receptor subunit GluR1 phosphorylated at Ser(845), which regulates AMPA receptor association with the plasma membrane, were reduced in a calcineurin-dependent manner in the presence of AβOs, and treatment with SKF81297 prevented this reduction. Establishing the functional relevance of these findings, SKF81297 blocked the impairment of long term potentiation induced by AβOs in hippocampal slices. Results suggest that D1/D5 receptors may be relevant targets for development of novel pharmacological approaches to prevent synapse failure in AD.     

Cytotoxic geranylflavonoids from Bonannia graeca

The analysis of the aerial parts of Bonannia graeca led to the isolation and characterization of polar geranylated flavonoids (6 and 7). The structure elucidation was performed by extensive spectroscopic methods (1D and 2D NMR) and comparison with literature data. All natural flavonoids isolated from B. graeca (1-7) and some synthetic derivatives (8-11) were tested for cytotoxic activity against four human tumor cell lines. Preliminary structure-activity relationship correlations are discussed.     

Tuber melanosporum: mating type distribution in a natural plantation and dynamics of strains of different mating types on the roots of nursery-inoculated host plants

? In light of the recent finding that Tuber melanosporum, the ectomycorrhizal ascomycete that produces the most highly prized black truffles, is a heterothallic species, we monitored the spatial distribution of strains with opposite mating types (MAT) in a natural truffle ground and followed strain dynamics in artificially inoculated host plants grown under controlled conditions. ? In a natural truffle ground, ectomycorrhizas (ECMs), soil samples and fruit bodies were sampled and genotyped to determine mating types. Simple sequence repeat (SSR) markers were also used to fingerprint ECMs and fruit bodies. The ECMs from nursery-inoculated host plants were analysed for mating type at 6 months and 19 months post-inoculation. ? In open-field conditions, all ECMs from the same sampling site showed an identical mating type and an identical haploid genotype, based on SSR analysis. Interestingly, the gleba of fruit bodies always demonstrated the same genotype as the surrounding ECMs. Although root tips from nursery-grown plants initially developed ECMs of both mating types, a dominance of ECMs of the same MAT were found after several months. ? The present study deepens our understanding of the vegetative and sexual propagation modes of T. melanosporum. These results are highly relevant for truffle cultivation.     

A new species of Heliocephala from Mexico with an assessment of the systematic positions of the anamorph genera Heliocephala and Holubovaniella

During a study of the microfungi on decaying leaves collected in México we encountered a fungus sharing features of the anamorph genera Heliocephala and Holubovaniella. This hyphomycete resembled Hol. elegans in possessing obclavate to fusiform, three-septate, rostrate phragmoconidia, but it can be distinguished by its much shorter, branched, determinate conidiophores. Unlike members of genus Heliocephala, which also possess determinant conidiophores, the phragmoconidia of this taxon are short-rostrate and have not been observed to germinate iteratively. Prompted by the discovery of this hyphomycete, we investigated the phylogenetic relationships among species of Heliocephala and Holubovaniella. Analysis of large subunit rDNA gene sequences positioned species of Heliocephala and Holubovaniella in the Dothideomycetes and identified Stomiopeltis betulae (Micropeltididaceae) as their closest relative. These results also indicated that Heliocephala and Holubovaniella are closely related taxa. Based on these findings and the similarity of the developmental and morphological characters of species of Heliocephala and Holubovaniella, we recognize these genera as synonymous and describe a new species, Heliocephala triseptata. A dichotomous key to the species of Heliocephala is provided.     

Non-equilibrium allele frequency spectra via spectral methods

A major challenge in the analysis of population genomics data consists of isolating signatures of natural selection from background noise caused by random drift and gene flow. Analyses of massive amounts of data from many related populations require high-performance algorithms to determine the likelihood of different demographic scenarios that could have shaped the observed neutral single nucleotide polymorphism (SNP) allele frequency spectrum. In many areas of applied mathematics, Fourier Transforms and Spectral Methods are firmly established tools to analyze spectra of signals and model their dynamics as solutions of certain Partial Differential Equations (PDEs). When spectral methods are applicable, they have excellent error properties and are the fastest possible in high dimension; see Press et al. (2007). In this paper we present an explicit numerical solution, using spectral methods, to the forward Kolmogorov equations for a Wright–Fisher process with migration of K populations, influx of mutations, and multiple population splitting events.     

Hematologic and plasma biochemical reference intervals for Morelet's crocodiles (Crocodylus moreletii) in the northern wetlands of Campeche, Mexico

Health surveys and hematologic and plasma biochemical analyses were conducted in 52 free-ranging and 51 captive Morelet's crocodiles (Crocodylus moreletii) in Campeche, Mexico, March-September 2007. Blood samples from 92 crocodiles (45 free-ranging and 47 captive) were collected for hematologic and plasma biochemical analyses. Average values of erythrocytes of free-ranging crocodiles were 1,046,166 cells/μl, and total white cells were 1.03 × 10(4) cells/μl. Captive crocodiles had erythrocyte and leukocyte values of 1,100,416 cells/μl and 8.51 × 10(3) cells/μl, respectively. There were no significant differences in values of erythrocytes or in hematocrit between free-ranging and captive crocodiles, or between sexes, or among size classes. Counts of leukocytes in free-ranging crocodiles were significantly higher than in captive individuals. The mean values of plasma analytes were 69.55 mg/l (glucose), 250.14 mg/l (cholesterol), 3.04 mg/l (uric acid), 2.70 mg/l (creatinine), and 20.20 IU/l (alanine aminotransferase). There were significant differences in cholesterol between free-ranging and captive crocodiles and between sexes.     

Galvanic vestibular stimulation improves the results of vestibular rehabilitation

Here, we present findings from a three-step investigation of the effect of galvanic vestibular stimulation (GVS) in normal subjects and in subjects undergoing vestibular rehabilitation (VR). In an initial study, we examined the body sway of 10 normal subjects after one minute of 2 mA GVS. The effect of the stimulation lasted for at least 20 minutes in all subjects and up to two hours in 70% of the subjects. We then compared a group of patients who received conventional VR (40 patients) with a group that received a combination of VR and GVS. Results suggest a significant improvement in the second group. Finally, we attempted to establish the optimal number of GVS sessions and to rule out a placebo effect. Fifteen patients received "systematic" GVS: five sessions, once a week. Five patients received "nonsystematic" galvanic stimulation in a sham protocol, which included two stimulations of the clavicle. These data were analyzed with Fisher's exact test and indicated that the best results were obtained after three sessions of GVS and no placebo effect was observed.     

The genetic diversity and phenotypic characterisation of Streptococcus agalactiae isolates from Rio de Janeiro, Brazil

Streptococcus agalactiae isolates are more common among pregnant women, neonates and nonpregnant adults with underlying diseases compared to other demographic groups. In this study, we evaluate the genetic and phenotypic diversity in S. agalactiae strains from Rio de Janeiro (RJ) that were isolated from asymptomatic carriers. We analysed these S. agalactiae strains using pulsed-field gel electrophoresis (PFGE), serotyping and antimicrobial susceptibility testing, as well as by determining the macrolide resistance phenotype, and detecting the presence of the ermA/B, mefA/E and lnuB genes. The serotypes Ia, II, III and V were the most prevalent serotypes observed. The 60 strains analysed were susceptible to penicillin, vancomycin and levofloxacin. Resistance to clindamycin, chloramphenicol, erythromycin, rifampin and tetracycline was observed. Among the erythromycin and/or clindamycin resistant strains, the ermA, ermB and mefA/E genes were detected and the constitutive macrolides, lincosamides and streptogramin B-type resistance was the most prevalent phenotype observed. The lnuB gene was not detected in any of the strains studied. We found 56 PFGE electrophoretic profiles and only 22 of them were allocated in polymorphism patterns. This work presents data on the genetic diversity and prevalent capsular serotypes among RJ isolates. Approximately 85% of these strains came from pregnant women; therefore, these data may be helpful in developing future prophylaxis and treatment strategies for neonatal syndromes in RJ.